Optimising cancer immunotherapy and emerging data supporting de-escalation strategies

Global cancer treatment costs are rising unsustainably, mainly due to drug expenses. Immunotherapeutics and molecular targeted drugs use increased dramatically in recent years, despite modest disease-specific survival gains and potential harm. Prescription rates for immune checkpoint inhibitor immunotherapy antibodies (ICIs) have multiplied. The global market for ICIs targeting the anti-programmed cell death-1 (PD1) receptor was US$40.5-48.7 billion in 2024 and continued rise is expected. Pembrolizumab (Keytruda) and Nivolumab (Opdivo) are the most prescribed anti-PD1 therapies, initially for melanoma and now across many tumours. Registration approvals vary from 1 year adjuvantly to open-ended duration for advanced cancer. Demand is high because ICIs can provide durable responses and improve survival, particularly for metastatic disease and in difficult-to-treat cancers. Use is also increasing in adjuvant settings though long-term survival benefits remain unproven. The trade-off for patients is repeated treatment visits, incurring personal costs and impaired activities of daily living in home and/or workplace. Furthermore, while ICIs are generally safe, significant healthcare costs occur in managing complex and life-threatening toxicities on or after treatment. Escalating expenditure is exacerbating inequalities of drug access globally. Evidence suggests current anti-PD1 dosing may be overtreatment. Pharmacokinetic and pharmacodynamic properties of ICIs differ from those of traditional cytotoxic drugs and higher ICI doses may not improve efficacy. Consequently, there is growing interest in de-escalation strategies to optimise care. Researchers design de-escalation trials to lower the amount of drug administered through decreasing dosage, frequency or duration. De-escalation aims to ease the burden on patients and healthcare systems.